Research of the unit is split between the identification of biologically active trace organic compounds isolated from natural sources and the mass spectrometry of biopolymers (e.g. peptide, proteins and oligonucleotides). A very close working relationship and collaboration is maintained with the Laboratory of Biophysical Chemistry, NHLBI. While this group runs many routine analyses for laboratories at NIH, as much emphasis as possible is placed on research using mass spectrometry for the structural elucidation of biologically active compounds. This year's key projects include: the structural identification of potent anti-HIV and anti-cancer compounds; the identification of post-translational modifications in proteins; continued research on cyanovirin, a potent anti-HIV compound heading towards clinical trial; development of techniques for micro- scale LCMS of biopolymers with the aim of greatly enhancing sensitivity; the identification and chiral determination of abnormal and modified amino acids as found in marine natural products; the identification of modified hemoglobins formed during treatments for sickle cell; and development of a method to follow protein folding using deuterium exchange. During the year the emphasis of all the research has become biopolymers and large proteins with multiple glycosylation sites and many overlapping disulfides and being examined. Attempts to define 3-D protein shapes using mass spectrometry are being developed. Multiple enzymatic digestion protocols and sophisticated software have been developed to assist the research and these are now in use worldwide. A new Q-TOF mass spectreometer shared with some other institutes has been ordered and this will drastically expand the biopolymer research potential of the group.